A Peyer's patch, which is an aggregate of lymph nodules covered with thin epithelial cells and exists in the jejunum or ileum, was reported by Peyer in 1677. It is one of protective organs against exogenous antigens such as bacteria. This protective system in the digestive tract mainly comprises secretory IgA (immunoglobulin A) produced and secreted in the intestinal mucosa. The production of this secretory IgA is controlled by the intestinal lymphoid tissue including Peyer's patches. This intestinal lymphoid tissue, which consists of the above-mentioned Peyer's patches, mesenteric lymph nodes, lamina propria mucosae, inter-epithelial cellular lymphocytes and plasma cells, is responsible for the local immunity independent of the systemic immunity. The epithelial cells involve chorioepithelium analogous to resorption epithelial cells and M cells (microholed cells) having thick and short microvilli. M cells, which were reported by Owen et al. in 1974, are now considered as an entrance into the digestive tract for exogenous antigens [Gastroenterology, 66, 189-203 (1974)].
Among antigens existing in the digestive tract, a specific one is selectively taken up or seized by M cells and the information thereof is transmitted to T cells via antigen presenting cells. The T cells comprise Th as the main component and the function thereof is controlled under the influences of various cytokines. The information of the antigen is further transmitted to B cells which will then differentiate into antibody-forming plasma cells. On the other hand, it is known that when a large amount of an antigen exists in the digestive tract for a prolonged period of time, an immunologically tolerant state is induced in the systemic immunity system via the function of suppressor T cells induced in Peyer's patches. Therefore it can be said that Peyer's patches play an important role not only in the local immunity but also in the systemic immunity.
Peyer's patches, which have the above-mentioned functions and are considered as the entrance of a route directly connected to the lymphatic system, may be regarded as the target sites of an immunomodulator such as an immunosuppressant or an immunopotentiator, an oral vaccine (a vaccine for oral administration), or an antigen aiming at oral desensitization (an attempt to reduce sensitization by oral administration).
As a conventional method for the administration of a physiologically active substance to Peyer's patches, there is known a method wherein are used hydrophobic and in vivo-degradable polymers such as in vivo-degradable polyesters (Japanese Patent Application Laid-Open Gazette No. 190833/88). This method comprises a technique for preparing microcapsules from a mixed solution of a high-molecular substance and a physiologically active substance which are dissolved in an organic solvent, by a submerged drying method. However, the physiologically active substances to be used for the above-mentioned purposes involve many hydrophilic substances such as polypeptides. Accordingly, the submerged drying method as described in the above Gazette is disadvantageous in that microcapsules having these hydrophilic substances encapsulated therein can be hardly prepared thereby.
It is an object of the present invention to provide a liposome composition whereby both of hydrophobic and hydrophilic physiologically active substances can be encapsulated and which has a high ability to migrate toward Peyer's patches.